It is important that pharmaceutical products be effective and safe. Even if a pharmaceutical product is effective and safe immediately after production, if the drug is easily decomposed or denatured during distribution, it is not effective and safe as a pharmaceutical product. Therefore, the stability of the drug is extremely important for pharmaceutical products.
In addition, to maintain effectiveness and safety of a pharmaceutical product, not only the effectiveness and safety of the active ingredient but also the properties of the pharmaceutical preparation, such as drug dissolution property in the body and the like, are extremely important. For example, when dissolution of the drug from the pharmaceutical preparation is too slow, the blood concentration of the drug does not reach an effective level, and the expected efficacy may not be sufficiently exhibited. On the other hand, when dissolution of the drug from the pharmaceutical preparation is too fast, the blood concentration of the drug increases rapidly, and the risk of side effects increases.
In other words, a pharmaceutical product is required to ensure stability and constant dissolution of drug, in addition to the effectiveness and safety.
Meanwhile, drug dissolution property is known to correlate to the solubility of a drug. That is, it is known that, in general, a lower solubility of a drug is associated with slower drug dissolution property.
Incidentally, benzimidazole derivative (I) having a strong angiotensin II receptor antagonistic activity
wherein R1 is a monocyclic nitrogen-containing heterocyclic group having a hydrogen atom that can be deprotonized, R2 is an esterified carboxyl group, and R3 is an optionally substituted lower alkyl, or a salt thereof (hereinafter to be sometimes referred to as compound (I)), particularly, a salt of (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylate (WO2005/080384) is a promising therapeutic drug for hypertension and the like.
However, the properties of a pharmaceutical preparation need to be adjusted to stabilize compound (I) because compound (I) is unstable in the neutral pH range, at which pharmaceutical preparations are generally produced. Nevertheless, the solubility of compound (I) is low at a pH range where compound (I) is stable.
It is therefore extremely difficult to simultaneously afford the stability and solubility of compound (I), and simultaneous achievement thereof is desired.